Mussel adhesive protein product and applications thereof in suppression of skin inflammations

ABSTRACT

Disclosed are applications of a mussel adhesive protein or preparations thereof in suppression of skin inflammations. Specifically disclosed are applications of a mussel adhesive protein, preparations thereof and applications thereof in dermatitis, eczema, skin ulcer, technologies related to burns (comprising skin grafting), perniones, surgical incisions, herpes, abrasions, scars, psoriasis, erythema multiforme, skin damage after radiotherapy, skin cancers, folliculitis, urticaria and drug eruption, and applications in sunburn, polymorphous light eruption, pathological alopecia (comprising hair transplant), acne vulgaris, rosacea (that is, acne rosacea), and the like, and applications in the treatment of otitis externa.

FIELD OF THE INVENTION

The present invention substantially relates to the technical field ofdrugs, cosmetics, medical products, disinfecting products, healthcareproducts, food, and household chemicals, and more specifically, relatesto a mussel adhesive protein product and a use thereof for inhibitingskin inflammation.

DESCRIPTION OF THE RELATED ART

As the first physiological barrier and the largest organ of human body,skin always participates in functional activities of the body, maintainsthe unity of opposites between the body and natural environment.Moreover, any abnormal conditions of the body could be reflected fromthe skin surface as well. Skin consists of epidermis, dermis andsubcutaneous tissues, and comprises numerous auxiliary organs, such asfollicle glands, sebaceous glands, finger nails, toe nails, bloodvessels, lymphatic ducts, nerves and muscles. Skin has almost perfectcapabilities of physiological protection, such as barrier function,perception function, body temperature regulation function, absorptionfunction, secretion and excretion function, etc., and plays a veryimportant role in maintaining the body health.

Inflammation is a defensive response by an organism to irritation, withmanifestations such as redness, swelling, heat, pain, and dysfunction.In an inflammatory process, on one hand, a damage factor directly orindirectly damages tissues and cells, and on the other hand, the damagefactor is diluted, killed and surrounded through inflammatory hyperemiaand exudation. At the same time, the damaged tissues are repaired andhealed through regeneration of parenchymal and interstitial cells.Therefore, it can be stated that inflammation is a unified process ofdamage and anti-damage.

Mussel adhesive protein (MAP), also known as Mytilus edulis foot protein(Mefp), is a special protein secreted by marine shellfish, such asMytilus edulis Linnaeus, Mytilus coruscus and Perna viridis. Mussels aretypically attached, in groups, to coastal reefs or ship bottom and havethe ability to resist wave impacts in coastal waters. In fact, musselscan be extremely firmly attached to a base of almost any material, suchas metals, wood, glass, etc. The main reason why mussels have the abovecharacteristic is that such a special adhesive protein can be producedand stored inside the byssus gland thereof. Mussels release the adhesiveprotein through byssus to a surface of a solid like rock, to form awater-proof bonding and consequently fix itself.

At present, 11 adhesive protein subtypes have been identified inmussels, including mefp-1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, thecollagens pre-COL-P, pre-COL-D, pre-COL-NG, and the mussel feet matrixproteins PTMP and DTMP (Yaoyao Zhu, et al., Advances in Marine Science,2014, 32 (4): 560-568). MAP has 2 structural characteristics: (1)comprising lysine, such that the protein carries a high loading ofpositive charge; (2) comprising 3,4-dihydroxyphenylalanine (DOPA,Levodopa). Human cells and tissues carry negative charges. MAP istightly bonded to the cells and tissues through the static interactionbetween its own positive charge and the negative charge of the humancells and tissues, thereby playing a role of protection and treatment.In addition, DOPA is oxidized to produce o-diquinone, which may becrosslinked with unoxidized DOPA to form a membrane or a reticularsupport, such that the proteins are attached to human body surface in atighter and firmer manner to play a protective role. MAP is amacromolecular protein, and it needs about 3-10 days to be completelydegraded in human body. It has superior ability to be attached to cellsand tissues, such that MAP is stable in a local part to continuouslyplay its role.

Despite the above characteristics of MAP, MAP products are applied in avery limited number of fields at present. The MAP production is mainlycontrolled by BD Biosciences from the U.S., Kollodis from South Korea,and Biopolymer from Sweden. However, these companies' products areeither directly used as an MAP solution or stored as a freeze-driedpowder and dissolved prior to use. Their applications are mainly limitedto micro-cellular bonding and tissue adhesive agents. There are alsoreports that MAP is used for fetal membrane repair, seawatercorrosion-resistant coating, cardiac drug carrier, etc.

SUMMARY OF THE INVENTION

One object of the present invention is to provide MAP products.

MAP used herein refers to one or a mixture of several selected from thegroup consisting of 11 MAP subtypes, including mefp-1, mefp-2, mefp-3,mefp-4, mefp-5, mefp-6, the collagens pre-COL-P, pre-COL-D, pre-COL-NG,and the mussel feet matrix proteins PTMP and DTMP, that are currentlyknown and purified from marine mussels, such as Mytilus edulis Linnaeus,Mytilus coruscus, and Perna viridis, in bivalve mollusks of Mytilidae.MAP used herein may have a pH value, in an aqueous solution, in a rangeof pH 1.0-7.0, and in particular, in a range of pH 3.0-6.5 for bettertherapeutic results thereof.

MAP used herein may be obtained using the following preparation methods,for example, a method for separating and purifying MAP by using mixedadsorption chromatography according to the Chinese Patent No.ZL200710179491.0, a method for purifying MAP by using carboxymethyl ionexchange chromatography according to the Chinese Patent No.ZL200710179492.5, and a method for separating and purifying MAP by usingsalting out and dialysis according to the Chinese Patent No.ZL200910087567.6.

MAP used herein may be in a form of solution or freeze-dried powder, andin particular, the MAP concentration in a product may be 0.1-15.0 mg/ml.When the concentration is overly low, MAP does not have a good effect,and when the concentration is overly high, it may cause cytotoxicity,skin irritation, etc., which is not favorable for treatment of skininflammations.

MAP used herein may also be combined with excipients to prepare a liquidformulation. An exemplary MAP liquid formulation is prepared bydissolving or diluting an MAP stock solution or freeze-dried powder to acertain concentration or pH value, and the solution used for dissolutionor dilution could be water, physiological saline, phosphate solution,acetate solution, borate solution, etc. MAP in the final product mayhave a pH value in a range of pH 1.0-7.0, and in particular, in a rangeof pH 3.0-6.5 for better therapeutic results thereof.

MAP used herein may also be combined with excipients to prepare a gelformulation. An exemplary MAP gel formulation is prepared by mixing anMAP solution or freeze-dried powder with a gel matrix material, and thegel matrix material may be one or any combination of cellulosederivatives, Carbomer and Alginates, gummi tragacanthae, gelatin,pectin, Carrageenan, gellan gum, starch, Xanthan gum, cationic guar gum,agar, noncellulosic polysaccharides, vinyl polymers, acrylic resins,polyvinyl alcohol and carboxyvinyl polymer.

MAP used herein may also be combined with excipients to prepare alotion. An exemplary MAP lotion is made by mixing an MAP solution orfreeze-dried powder with a lotion matrix, and said lotion matrix maycomprise one or any combination of cellulose derivatives, glycerin,noncellulosic polysaccharides, and propanediol.

MAP used herein may also be combined with excipients to prepare a paste.An exemplary MAP paste is made by mixing MAP with a paste matrixmaterial, and said paste matrix material may comprise glycerin,vaseline, paraffin, etc.

Those skilled in the art may choose the above formulations or otherappropriate formulations according to characteristics of clinicalindications and skin damage at different stages.

MAP used herein may further be combined with a matrix material toprepare a dressing or a therapy patch for application on a skin surface.The liquid of an exemplary MAP therapy patch may be an MAP solution or acombination thereof with one or more of cellulose derivatives, Carbomerand Alginates, gummi tragacanthae, gelatin, pectin, Carrageenan, gellangum, starch, Xanthan gum, cationic guar gum, agar, noncellulosicpolysaccharides, vinyl polymers, acrylic resins, polyvinyl alcohol orcarboxyvinyl polymer, gelatin, isinglass, pectin, alginates, glycerin,vaseline, paraffin, polyethylene glycol, vitamins, and glutathione. Theabove MAP solution or composition impregnates a matrix material, such asgauze, non-woven cloth, or silk paper, and the therapy patch may be, forexample, band-aid, facial mask, eye mask, hand mask, foot mask, etc.

MAP used herein may also be prepared into a foam formulation. Anexemplary MAP foam formulation is made by mixing an MAP solution orfreeze-dried powder with a foaming agent matrix, and said foaming agentmatrix material may comprise one or any combination of hydroxypropylmethyl cellulose, gelatin, polyethylene glycol, sodium dodecyl sulfate,sodium fatty alcohol polyoxyethylene ether sulfonate, corn gluten powderand acrylamide. A particular advantage is that the foaming agentreleases pressure during the defoaming process, which is more favorablefor attachment, permeation and onset of MAP at an affected part. At thesame time, the foaming agent has a long defoaming time, which extendsthe action time and makes the MAP onset more significant.

Components known in the art to be capable of strengthening moisturizingand anti-oxidation capabilities, such as glycerin, polyethylene glycol,vitamins, and glutathione, may be further added into the above variousproducts that contain MAP to further improve the moisturizing andanti-oxidation capabilities.

All the above formulations may be prepared with methods known in theart, and reference may be made to, for example, “PharmaceuticalPreparation”, for detailed operating steps.

MAP used herein may be used as a main raw material to prepare a drugalong with a pharmaceutically acceptable carrier. The drug may be aliquid formulation, a gel formulation, a lotion, a paste, a therapypatch, or a foam formulation. The drug may be applied externally, and inparticular, may be applied on the skin externally.

MAP used herein may be used as a main raw material to prepare a medicaldevice. The term used herein, medical device, refers to a material, orother similar or related objects, used, directly or indirectly, on humanbody. The medical device may be a liquid formulation, a gel formulation,a lotion, a paste, a therapy patch, or a foam formulation. The medicaldevice may be applied externally, and in particular, may be applied onthe skin externally.

MAP used herein may be used as a main raw material to prepare cosmeticsalong with excipients that are acceptable in the field of cosmetics. Thecosmetics may be a liquid formulation, a gel formulation, a lotion, apaste, a therapy patch, or a foam formulation. The cosmetics may beapplied externally, and in particular, may be applied on the skinexternally.

MAP used herein may be used as a main raw material to prepare adisinfecting product along with excipients that are acceptable in thefield of disinfecting products. The term used herein, disinfectingproduct, refers to a disinfectant, a disinfecting device, a sanitaryproduct and a disposable medical article that kills or eliminatespathogenic microorganisms in the environment in a chemical, physical orbiological manner. The disinfecting product may be a liquid formulation,a gel formulation, a lotion, a paste, a therapy patch, or a foamformulation. The disinfecting product may be applied externally, and inparticular, may be applied on the skin externally.

MAP used herein may be used as a main raw material to prepare ahealthcare product or food along with excipients that are acceptable inthe field of healthcare products or foods. The healthcare product orfood may be a liquid formulation, a gel formulation, a lotion, a paste,a therapy patch, or a foam formulation. The healthcare product or foodmay be applied externally or edible, and in particular, may be appliedon the skin externally.

MAP used herein may be used as a main raw material to prepare ahousehold chemical along with excipients that are acceptable in thefield of household chemicals. The term used herein, household chemicals,refers to a chemical product for daily use, including shampoo, bath gel,etc. The household chemical may be a liquid formulation, a gelformulation, a lotion, a paste, a therapy patch, or a foam formulation.The household chemical may be applied externally, and in particular, maybe applied on the skin externally.

Another object of the present invention is to provide a use of MAPproducts in inhibiting skin inflammation.

The term used herein, inhibit, refers to a process that mitigates theoriginal damages after a tissue or organism is irritated. The term usedherein, treat, refers to a process that intervenes or changes a specifichealth state and activities taken to relief suffering.

Skin inflammation is a skin disease and one of the common diseases andfrequently-occurring diseases that severely affect human health. Whenthe skin's barrier function is weakened, inflammations inside the skin,such as coarseness, redness, itching, eczema, and dryness, will occur,and the causes are external and internal. Internal causes involve bodyconditions, hormone level, pressure, etc.; external causes include, forexample, UV, allergens, heat and other irritations. Only throughtreatments that inhibit the inflammation, can the skin condition beimproved.

Small lumps, refractory ulcers, and pigmented spots caused by skininflammation, if not treated promptly, will develop to basal cellcarcinoma, squamous cell carcinoma, and malignant melanoma. Basal cellcarcinoma and squamous cell carcinoma are just some small spots withcoarse surface in the beginning, which are slightly redder or whiterthan surrounding skin, or may be tiny lumps or small ulcers that tend tobleed, are slow to heal, or do not heal. Early symptoms of malignantmelanoma usually include the appearance of skin pigmented spots, changeof mole colors, appearance of new moles, and the production of brown andblack pigment cells due to pathological accumulation.

Dermatitis is a general term for skin inflammatory diseases caused byvarious internal and external infectious or non-infectious factors, andits causes of disease and clinical manifestations are complex anddiversified. Clinically, a certain dermatitis is often defined to be acertain dermatitis according to the cause of disease, disease locationor other clinical features. For example, dermatitis caused by contactwith a substance is referred to as contact dermatitis, dermatitis causedby internal use of a drug is referred to as dermatitis medicamentosa,etc.

Eczema is a skin inflammatory reaction with strong itching caused by avariety of internal and external factors. It has three phases, acute,sub-acute, and chronic. In the acute phase, there is a tendency ofexudation, while the chronic phase includes infiltration andhypertrophy. Some patients directly have chronic eczema. Skin lesionshave characteristics such as multi-form, symmetric, itchy and easilyrecurring.

Skin ulcer is a common disease and frequently-occurring disease insurgery of traditional Chinese medicine, which is a topical disease withulcers on the skin as the main clinical manifestation, inability to healfor a long period as clinical feature, and with skin tissues missing,damaged, liquefied, infected, and necrotic. As the ulcerated surface ishard to heal and costly, it causes great mental pressure and economicloss to the patients, and severely affects the body health and lifequality of the patients.

Herpes refers, in a broad sense, to diseases caused by viruses inherpetoviridae. At present, it is known that eight viruses in thisfamily could infect humans, and these viruses are collectively referredto as human herpes viruses. Among them, the common ones includevaricella zoster virus, herpes simplex virus, etc., and herpes couldinfect a number of human organs.

Acne is a follicular (pilosebaceous unit) chronic, inflammatory skindisease, the occurrence of which is closely related to main factors likehypersteatosis, blocked pilosebaceous ducts, bacterial infection andinflammatory reaction. It tends to occur in youth, and would oftennaturally mitigate or heal after puberty. Clinical manifestations arecharacterized by multiform skin lesions on the face, such as pimple,rash, pustule, nodus, etc.

Hives is a localized edema reaction due to expansion of skin and mucosalsmall vessels and increased permeability, which typically subsideswithin 2 to 24 hours, but will recur to produce new skin rashes. Thecauses of hives are very complicated, and causes cannot be identifiedfor about ¾ of the patients, in particular in the case of chronic hives.Common causes mainly include: Food and food additives; inhaledsubstances; infection; drugs; physical factors, such as mechanicalirritation, coldness and heat, sunshine, etc.; insect bites; mentalfactors and endocrine changes; genetic factors, etc.

Polymorphous sunlight eruption or polymorphous light eruption is aphotoallergic reaction, which is a recurrent, chronic, multiform, andphotosensitive skin disease. Currently, it is believed that this mightbe a delayed photoallergy caused by a variety of reasons. A variety ofphoto-allergens are involved with this.

Early manifestations of skin cancers are mostly erythema-like skinlesions, accompanied by scaly desquamation or crust formation. It isdifficult to differentiate its histological type through observationwith naked eye only, and moreover, it tends to be mistaken as benignskin diseases like psoriasis, eczema. The diagnosis can be confirmedoften through pathologic examination. Skin cancers have a low incidencerate in China, but are one of the common malignant tumors among whitepeople. Basal cell carcinoma is the most common skin cancer.

Psoriasis, commonly known as serpedo, is a chronic, inflammatory skindisease with a relatively long course of disease and tendency to recur.Some patients almost never heal in their entire life. Clinicalmanifestations of psoriasis mainly include erythema and scales. It couldoccur over the whole body, more commonly seen on scalp and limbextension sides.

Burns usually refer to tissue damages caused by heat, including hotliquids (water, soup, oil, etc.), steam, high-temperature gases, flame,red-hot metal liquid or solid (e.g. melted steel, steel ingot), and thetissues mainly refer to skin and/or mucosa, and in serious cases,subcutaneous and/or submucous tissues, such as muscles, bones, joints,and even internal organs, could be damaged.

Frostbite means recurrent erythema and swelling damage on local skincaused by cold weather, and in serious cases, blisters and ulcers couldappear. The course of the disease is slow, and it heals on its own whenthe weather becomes warm, but tends to recur.

Operative incision refers to skin damage caused by surgeries.

Bruise is an injury caused by friction due to a blunt mechanical force,with epidermis peeled off and rolled as the main manifestation. It maypresent with scratches, scores, percussion marks, pressing marks,pressing and scratching marks, etc.

Scar is a general term of histopathological changes to the morphology ofnormal skin tissues caused by various traumas, which is a necessaryproduct from the process of repairing human body traumas. When the scargrowth exceeds a certain limit, various complications will take place,e.g. destruction to the appearance, dysfunctions, movement disorders,etc., in particular in the case of scars from burning, scalding, andsevere injuries.

Erythema multiforme is an acute inflammatory skin disease, which isself-limited. The rash is multiform, including erythema, papule, hive,blister, etc. The characteristic skin lesion is a target lesion, i.e.iris lesion. There are various degrees of mucosal damages, and damagesto internal organs in some cases.

Post radiation therapy skin damage means skin ulceration due toradiation therapy.

Folliculitis is a suppurative inflammation due to bacterial infection ofthe entire hair follicle. At the beginning, red papules appear, whichgradually evolve into papular pustules. They are isolated and can feelslight pain. For adults, it mostly occurs in hairy positions, and forchildren, it tends to occur on the head. The rashes sometimes join eachother, and small bald patches could form after healing.

Pathological alopecia is hair loss caused by pathological factors, suchas some mental pressures, acute or chronic contagious diseases, variousskin diseases, endocrine disorder, physical or chemical factors, neuralfactors, nutrition factors, etc.

Seborrheic dermatitis is also referred to as seborrheic eczema, which isa chronic, papulosquamous and inflammatory skin disease that occurs atpositions with a lot of sebaceous glands. The skin lesion mostly beginsat the scalp, and gradually spread downwards to eyebrow, nasolabialfold, cheek, behind the ears, upper chest, intrascapular area,periumbilical area, genital area, groin, etc.

External otitis is a chronic, localized and suppurative disease ofexternal auditory meatus skin, also referred to as localized externalotitis. It occurs at the cartilage part of external auditory meatus, andis one of the common otologic diseases. External otitis is mostly causedby damages to the external auditory meatus skin as a result of earpicking or by water accumulation in the external auditory meatus duringswimming or showering, such that local epidermis is softened and proneto bacterial infection.

Surprisingly, the inventors find that MAP has excellent effects onmitigating erythema, redness and swelling, edema, blisters, and bullouspemphigoid caused by various skin inflammations, inhibiting exudation ofsubcutaneous tissue fluid, mitigating coarse pores, and suppressingitching and pain caused by inflammations.

Surprisingly, the inventors find that MAP can be used to treatdermatitis, eczema, sunburn, polymorphous sunlight eruption, skin ulcer,burn surgery (including skin grafting), frostbite, operative incision,herpes, bruise, scar, psoriasis, erythema multiforme, post radiationtherapy skin damage, skin cancer, seborrheic dermatitis, pathologicalalopecia (including skin grafting), regular acne, acne rosacea (i.e.brandy nose), folliculitis, hives, drug eruption, polymorphous sunlighteruption, and external otitis.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates results of herpes zoster treatment with the MAPliquid medical device according to the present invention and thecontrol, wherein A, patients before the treatment; B, patients at 2weeks after the treatment.

FIG. 2 illustrates the pain relief effect of the MAP liquid healthcareproduct according to the present invention in scar pain relieftreatment.

FIG. 3 illustrates the effect of the MAP liquid medical device accordingto the present invention in promoting wound surface healing in treatmentof chronic skin ulcers, wherein A, patients at Day 0 of the treatment;B, the treatment method for the patients; C, patients at Day 7 of thetreatment; D, patients at Day 10 of the treatment; E, patients at Day 15of the treatment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Embodiments of the present invention comprise:

1. Use of MAP in treatment of skin inflammation.

2. The use of MAP according to Embodiment 1, wherein the MAP is one or amixture of several selected from the group consisting of subtypesmefp-1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, the collagens pre-COL-P,pre-COL-D, pre-COL-NQ the mussel feet matrix proteins PTMP and DTMP.

3. The use of MAP according to Embodiment 1, wherein the MAPconcentration may be 0.1-15.0 mg/ml.

4. The use of MAP according to Embodiment 1, wherein the MAP may be aliquid formulation, a gel formulation, a lotion, a paste, a therapypatch, or a foam formulation in use.

5. The use of MAP according to Embodiment 1, wherein MAP in the finalproduct is in a range of pH 1.0-7.0, and in particular, in a range of pH3.0-6.5.

6. The use of MAP according to any one of Embodiments 1-5, wherein theskin inflammation is selected from: dermatitis, eczema, skin ulcer, burnsurgery (including skin grafting), frostbite, operative incision,herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skincancer, folliculitis, hives, and drug eruption.

7. The use of MAP according to any one of Embodiments 1-5, wherein theskin inflammation is selected from: sunburn, polymorphous sunlighteruption, pathological alopecia (including hair transplant), regularacne, and acne rosacea (i.e. brandy nose).

8. The use of MAP according to any one of Embodiments 1-5, wherein theskin inflammation is external otitis.

9. Use of MAP as an active ingredient in a composition for treatment ofskin inflammation, wherein the composition is a liquid formulation, agel formulation, a lotion, a paste, a therapy patch, or a foamformulation in use.

10. The use of MAP according to Embodiment 9, wherein the composition isa composition for external application on the skin.

11. A drug for treatment of skin inflammation, comprising MAP and apharmaceutically acceptable carrier, wherein the MAP concentration is0.1-15.0 mg/ml.

12. A medical device for treatment of skin inflammation, comprising MAPand a carrier acceptable in the field of medical devices, wherein theMAP concentration is 0.1-15.0 mg/ml.

13. A cosmetic for treatment of skin inflammation, comprising MAP and acarrier acceptable in the field of cosmetics, wherein the MAPconcentration is 0.1-15.0 mg/ml.

14. A disinfecting product for treatment of skin inflammation,comprising MAP and a carrier acceptable in the field of disinfectingproducts, wherein the MAP concentration is 0.1-15.0 mg/ml.

15. A healthcare product or food for treatment of skin inflammation,comprising MAP and a carrier acceptable in the field of healthcareproducts or foods, wherein the MAP concentration is 0.1-15.0 mg/ml.

16. A household chemical for treatment of skin inflammation, comprisingMAP and a carrier acceptable in the field of household chemicals,wherein the MAP concentration is 0.1-15.0 mg/ml.

17. Use of MAP in a drug for treatment of skin inflammation, wherein theskin inflammation is selected from: dermatitis, eczema, skin ulcer, burnsurgery (including skin grafting), frostbite, operative incision,herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skincancer, folliculitis, hives, and drug eruption.

18. Use of MAP in a drug for treatment of skin inflammation, wherein theskin inflammation is selected from: sunburn, polymorphous sunlighteruption, pathological alopecia (including hair transplant), regularacne, and acne rosacea (i.e. brandy nose).

19. Use of MAP in a drug for treatment of skin inflammation, wherein theskin inflammation is external otitis.

20. Use of MAP in a medical device for treatment of skin inflammation,wherein the skin inflammation is selected from: dermatitis, eczema, skinulcer, burn surgery (including skin grafting), frostbite, operativeincision, herpes, bruise, scar, psoriasis, erythema multiforme, chemorash, skin cancer, folliculitis, hives, and drug eruption.

21. Use of MAP in a medical device for treatment of skin inflammation,wherein the skin inflammation is selected from: sunburn, polymorphoussunlight eruption, pathological alopecia (including hair transplant),regular acne, and acne rosacea (i.e. brandy nose).

22. Use of MAP in a medical device for treatment of skin inflammation,wherein the skin inflammation is external otitis.

23. Use of MAP in a cosmetic for treatment of skin inflammation, whereinthe skin inflammation is selected from: dermatitis, eczema, skin ulcer,burn surgery (including skin grafting), frostbite, operative incision,herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skincancer, folliculitis, hives, and drug eruption.

24. Use of MAP in a cosmetic for treatment of skin inflammation, whereinthe skin inflammation is selected from: sunburn, polymorphous sunlighteruption, pathological alopecia (including hair transplant), regularacne, and acne rosacea (i.e. brandy nose).

25. Use of MAP in a cosmetic for treatment of skin inflammation, whereinthe skin inflammation is selected from: external otitis.

26. Use of MAP in a disinfecting product for treatment of skininflammation, wherein the skin inflammation is selected from:dermatitis, eczema, skin ulcer, burn surgery (including skin grafting),frostbite, operative incision, herpes, bruise, scar, psoriasis, erythemamultiforme, chemo rash, skin cancer, folliculitis, hives, and drugeruption.

27. Use of MAP in a disinfecting product for treatment of skininflammation, wherein the skin inflammation is selected from: sunburn,polymorphous sunlight eruption, pathological alopecia (including hairtransplant), regular acne, and acne rosacea (i.e. brandy nose).

28. Use of MAP in a disinfecting product for treatment of skininflammation, wherein the skin inflammation is external otitis.

29. Use of MAP in a healthcare product or food for treatment of skininflammation, wherein the skin inflammation is selected from:dermatitis, eczema, skin ulcer, burn surgery (including skin grafting),frostbite, operative incision, herpes, bruise, scar, psoriasis, erythemamultiforme, chemo rash, skin cancer, folliculitis, hives, and drugeruption.

30. Use of MAP in a healthcare product or food for treatment of skininflammation, wherein the skin inflammation is selected from: sunburn,polymorphous sunlight eruption, pathological alopecia (including hairtransplant), regular acne, and acne rosacea (i.e. brandy nose).

31. Use of MAP in a healthcare product or food for treatment of skininflammation, wherein the skin inflammation is selected from: externalotitis.

32. Use of MAP in a household chemical for treatment of skininflammation, wherein the skin inflammation is selected from:dermatitis, eczema, skin ulcer, burn surgery (including skin grafting),frostbite, operative incision, herpes, bruise, scar, psoriasis, erythemamultiforme, chemo rash, skin cancer, folliculitis, hives, and drugeruption.

33. Use of MAP in a household chemical for treatment of skininflammation, wherein the skin inflammation is selected from: sunburn,polymorphous sunlight eruption, pathological alopecia (including hairtransplant), regular acne, and acne rosacea (i.e. brandy nose).

34. Use of MAP in a household chemical for treatment of skininflammation, wherein the skin inflammation is external otitis.

35. A foam formulation for treatment of skin inflammation, comprisingMAP as the main active ingredient and a foaming agent matrix material,said foaming agent matrix material being one or any combination ofhydroxypropyl methyl cellulose, gelatin, polyethylene glycol, sodiumdodecyl sulfate, sodium fatty alcohol polyoxyethylene ether sulfonate,corn gluten powder and acrylamide, wherein the MAP concentration is0.1-15.0 mg/ml.

The present invention will be further described below with reference tospecific embodiments. It should be noted that, when a drug, medicaldevice, cosmetic, disinfecting product, healthcare product or food, orhousehold chemical formed from MAP or various formulations of MAPaccording to the present invention is applied on a subject, it can beused on the indications described above and exhibits the functionsdescribed above. All formulations within the scope of the presentinvention have been tested, and only a small portion thereof isdescribed below in the embodiments for the purpose of description;however, they shall not be construed as limitations to the presentinvention.

Unless otherwise specifically described, all reagents used in thepresent invention are commercially available on the market.

EXAMPLE 1 Use of MAP Liquid Medical Device in Treatment of Eczema

Take 1 ml of an MAP solution with concentration at 20.0 mg/ml, add 9 mlof 0.1% citric acid solution, and prepare an MAP aqueous solutionmedical device with concentration at 2.0 mg/ml.

Gather 20 patients with acute eczema as diagnosed by dermatologists fortest. Eczema locations are not limited for the selected patients, theaffected areas are 1-2% TBSA (total body surface area), and the affectedareas have patches of erythema, dense or dispersed small papules andblisters, or large patches of weeping liquid and ulceration.

For the selected patients, spray the above MAP aqueous solution medicaldevice on the affected part, 3 times per day, and spray 3-5 times eachtime until the affected part is completely covered by the MAP aqueoussolution medical device. After sprayed with the MAP aqueous solutionmedical device, itching at the affected part is significantly reducedwithin 2 to 10 min, the visual analogue score VAS goes from 6.0-8.0prior to the drug administration down to 1.0-3.0, and the duration ofitching relief can last 2 to 10 h (see Table 1). As the time of drug useis extended, the itching relief duration is extended, and the useinterval is extended, which does not show any drug dependence.

After 3 days of continuous spraying of MAP, 4 patients have their eczemaareas fully healed, as indicated by disappearance of erythema, papulesand blisters, and no exudation at the affected part. After 5 days ofcontinuous spraying, all patients are cured.

TABLE 1 Average onset time (min) 3.3 ± 1.2 Average VAS prior to use 7.6± 0.9 Average VAS after use 1.4 ± 0.3 Average itching relief 8.2 ± 2.1duration (h) Average healing time (d) 3.9 ± 1.0

EXAMPLE 2 Use of MAP Gel Medical Device in Treatment of Eczema

Add 10 g sodium carboxymethyl cellulose into 20 ml deionized water,place in a bath at 90° C. for 30 min until complete dissolution toobtain a gel matrix. Add 2.5 ml of an MAP solution with concentration at10.0 mg/ml into the gel matrix, add slowly under constant stirring, andmix homogeneously to form an MAP gel medical device, wherein the MAPconcentration is 1.1 mg/ml.

Gather 20 patients with acute eczema. Eczema locations are not specifiedfor the selected patients, the affected areas are 1-2% TBSA (total bodysurface area). The patients are diagnosed by dermatologists, sign theinformed consent form, and then join the clinical test. The affectedareas of the patients have patches of erythema, dense or dispersed smallpapules and blisters, or large patches of weeping liquid and ulceration.

For the selected patients, apply the above MAP gel medical device on theaffected part, 3 times per day, and spray 3-5 times each time until theaffected part is completely covered by the MAP gel medical device. Afterapplied with the MAP gel medical device, itching at the affected part issignificantly reduced within 1 to 7 min, the visual analogue score VASgoes from 7.0-8.0 prior to the drug administration down to 1.0-2.0, andthe duration of itching relief can last 2 to 8 h. As the time of druguse is extended, the itching relief duration is extended, and the useinterval is extended, which does not show any drug dependence.

After 3 days of continuous application of the MAP gel medical device, 8patients have their eczema areas fully healed, as indicated bydisappearance of erythema, papules and blisters, and no exudation at theaffected part. After 5 days of continuous spraying, all patients arecured (see Table 2).

TABLE 2 Average onset time (min) 3.8 ± 2.1 Average VAS prior to use 7.7± 0.5 Average VAS after use 1.3 ± 0.2 Average itching relief 6.9 ± 2.1duration (h) Average healing time (d) 3.2 ± 1.0

EXAMPLE 3 Use of MAP Gel Cosmetic in Treatment of Polymorphous SunlightEruption

Take an MAP solution with concentration at 0.5 mg/ml, mix withpolyethylene glycol and glycerin at a volumetric ratio of 2:1:2, thenadd water for injection in an equal volume to prepare an MAP gelcosmetic, wherein the MAP content is 0.1 mg/g.

Gather 10 patients with acute inflammatory reaction after sunbath, it isrequired that the affected parts of the selected patients include theface or limbs, and the affected areas are no smaller than 1% TBSA (totalbody surface area). The patients are diagnosed by dermatologists fortest. The affected parts of the selected patients have erythema, edemaor blisters. Apply the above MAP gel cosmetic at the affected part for 3times per day, and evenly apply the gel on the surface of the affectedpart each time. After applied with the MAP gel cosmetic, mitigation ofitching and pain occurs to all the 10 patients, the onset time variesfrom 3 to 20 min, and the itching or pain relief duration is 3-8 h afteruse. After applying the MAP gel cosmetic for 5 days, all the 10 patientsof sunlight eruption have their affected parts healed. Erythema, edemaor blisters disappear (see Table 3).

TABLE 3 Average onset time (min) 12.6 ± 3.7  Average VAS prior to use4.9 ± 0.8 Average VAS after use 1.1 ± 0.4 Average itching relief 5.6 ±1.7 duration (h) Average healing time (d) 4.0 ± 0.6

EXAMPLE 4 Use of MAP Lotion Medical Device in Treatment of PolymorphousSunlight Eruption

Take an MAP solution with concentration at 2.0 mg/ml, mix withpropanediol and glycerin at a volumetric ratio of 1:1:2, then add waterfor injection in an equal volume to prepare an MAP lotion medicaldevice, wherein the MAP content is 0.25 mg/g.

Gather 10 patients with acute inflammatory reaction after sunbath, it isrequired that the affected parts of the selected patients include theface or limbs, and the affected areas are no smaller than 1% TBSA (totalbody surface area). The patients are diagnosed by dermatologists fortest. The affected parts of the selected patients have erythema, edemaor blisters. Apply the above MAP lotion medical device at the affectedpart for 3 times per day, and evenly apply the household chemical lotionon the surface of the affected part each time. After applied with theMAP lotion medical device, mitigation of itching and pain occurs to allthe 10 patients, the onset time varies from 2 to 18 min, and the itchingor pain relief duration is 3-10 h after use. After applying the MAPhydrogel cosmetic for 4 days, all the 10 patients of sunlight eruptionhave their affected parts healed. Erythema, edema or blisters disappear(see Table 4).

TABLE 4 Average onset time (min) 10.2 ± 2.6  Average VAS prior to use5.2 ± 1.6 Average VAS after use 1.0 ± 0.7 Average itching relief 6.6 ±1.3 duration (h) Average healing time (d) 3.5 ± 0.7

EXAMPLE 5 Use of MAP Hydrogel Medical Device in Treatment of Deep SecondDegree Burn

Take an MAP solution, mix with Guar gum, propanediol and propanetriol ata volumetric ratio of 4:1:1:1, add water for injection, use citric acidto adjust to pH 5.0, and prepare an MAP hydrogel medical device with theMAP content at 1.5 mg/ml.

Gather 30 patients of deep second degree burn, it is required that morethan two doctors jointly confirm that the patients have deep seconddegree burn, and the patients sign the informed consent form and thenjoin the study. The total burn area is less than 30% TBSA (total bodysurface area), and the tested part has an area greater than 2% TBSA. Usethe above MAP gel medical device (test group) and a commercial chitosangel (control group) as a control to treat, randomly, the subjects. Bothproducts are used once every other day in an amount that can evenlycover the affected part. All the wounds need to be thoroughly cleanedwith a disinfectant prior to the use of the product for the test groupand the control product.

Observe the redness and swelling (wound edge width) of wound edges ofthe wounds in the test group and the control group at the same day (Day0) of joining the study, Days 4, 6, 10, and 14, respectively, andperform analysis using the chi-square test. In the case where the testlevel a is 0.05, the differences on Days 10 and 14 are statisticallysignificant (see Table 5). It is believed that the MAP hydrogel medicaldevice according to the present invention is better than the controlproduct in mitigating redness and swelling. At the same time, it isfurther observed that the MAP hydrogel medical device according to thepresent invention has the effect of inhibiting exudation in the acuteinflammation phase of burns and lowering the probability of growth ofmicroorganisms.

TABLE 5 Index Test group Control group P value Day 0 0.7640 None  4 (26.67% ) 5 ( 33.33% ) Light  4 ( 26.67% ) 2 ( 13.34% ) Mild  3 ( 20.00%) 4 ( 26.67% ) Severe  4 ( 26.67% ) 4 ( 26.67% ) Day 4 0.6895 None  5 (33.33% ) 6 ( 40.00% ) Light  5 ( 33.33% ) 4 ( 26.67% ) Mild  4 ( 26.67%) 1 ( 6.67% )  Severe 1 ( 6.67% ) 4 ( 26.67% ) Day 6 1.0083 None  5 (33.33% ) 7 ( 46.70% ) Light  6 ( 40.00% ) 3 ( 20.00% ) Mild  3 ( 20.00%) 2 ( 13.33% ) Severe 1 ( 6.67% ) 3 ( 20.00% ) Day 10 0.0429 None 12 (80.00% ) 8 ( 53.33% ) Light  2 ( 13.34% ) 2 ( 13.34% ) Mild 1 ( 6.67% )5 ( 33.33% ) Severe 0 ( 0.00% ) 0 ( 0.00% )  Day 14 0.0376 None 13 (86.67% ) 7 ( 46.70% ) Light  2 ( 13.34% ) 3 ( 20.00% ) Mild 0 ( 0.00% )5 ( 33.33% ) Severe 0 ( 0.00% ) 0 ( 0.00% ) 

EXAMPLE 6 Use of MAP Liquid Drug in Treatment of Deep Second Degree Burn

Take an MAP solution with concentration at 5 mg/ml, add 0.001% aceticacid in an equal volume to dilute to 2.5 mg/ml, the pH of the solutionis 5.0, and form an MAP liquid drug with an MAP content of 2.5 mg/ml.

Gather 30 patients of deep second degree burn, it is required that morethan two doctors jointly confirm that the patients have deep seconddegree burn, and the patients sign the informed consent form and thenjoin the study. The total burn area is less than 30% TBSA (total bodysurface area), and the tested part has an area greater than 2% TBSA. Usethe above MAP liquid drug (test group) and a commercial chitosan liquidproduct (control group) as a control to treat, randomly, the subjects.Both products are used once every other day in an amount that can evenlycover the affected part. All the wounds need to be thoroughly cleanedwith a disinfectant prior to the use of the product for the test groupand the control product.

Observe the redness and swelling (wound edge width) of wound edges ofthe wounds in the test group and the control group at the same day (Day0) of joining the study, Days 4, 6, 10, and 14, respectively, andperform analysis using the chi-square test. In the case where the testlevel a is 0.05, the difference on Day 10 is statistically significant(see Table 6). It is believed that the MAP liquid drug according to thepresent invention is better than the control product in mitigatingredness and swelling. At the same time, it is further observed that theMAP liquid drug has the effect of inhibiting exudation in the acuteinflammation phase of burns and lowering the probability of growth ofmicroorganisms.

TABLE 6 Index Test group Control group P value Day 0 0.9592 None  4 (26.67% ) 5 ( 33.33% ) Light  4 ( 26.67% ) 2 ( 13.34% ) Mild  3 ( 20.00%) 4 ( 26.67% ) Severe  4 ( 26.67% ) 4 ( 26.67% ) Day 4 1.0743 None  6 (40.00% ) 6 ( 40.00% ) Light  5 ( 33.33% ) 3 ( 20.00% ) Mild  3 ( 20.00%) 2 ( 13.34% ) Severe 1 ( 6.67% ) 4 ( 26.67% ) Day 6 0.8739 None  7 (46.70% ) 7 ( 46.70% ) Light  5 ( 33.33% ) 3 ( 20.00% ) Mild  3 ( 20.00%) 2 ( 13.33% ) Severe 0 ( 0.00% ) 3 ( 20.00% ) Day 10 0.0420 None 11 (73.33% ) 8 ( 53.33% ) Light  3 ( 20.00% ) 2 ( 13.34% ) Mild 1 ( 6.67% )5 ( 33.33% ) Severe 0 ( 0.00% ) 0 ( 0.00% ) 

EXAMPLE 7 Use of MAP Liquid Medical Device in Treatment of Shingles

Take an MAP solution, dilute with physiological saline, use acetic acidto adjust to pH 4.0, and obtain an MAP liquid medical device, whereinthe MAP concentration is 5 mg/ml.

Select 15 patients of shingles, it is required that the affected areasare greater than 1% TBSA, the patients have a pain score ≥4, and theyare diagnosed by dermatologists before joining the study. Spray the MAPliquid medical device above at the affected part for 4 times per day.After sprayed with the MAP liquid medical device, the feeling of pain isweakened at the affected part within 1 min, and the duration of painrelief can last for 1.8 to 3 h on the 1st day of the use of the device.After 5 days of continuous spraying, the duration of pain relief isextended to 15 h, and the use interval is extended. After 7 days ofcontinuous spraying of the MAP liquid medical device above, erythema andblisters of shingles on 9 patients disappear, and their skin lesionsheal. After 14 days, erythema and blisters disappear for the other 6patients, and their skin lesions heal (see FIG. 1).

EXAMPLE 8 Use of MAP Hydrogel Disinfecting Product in Treatment ofShingles

Take an MAP solution, mix with Guar gum and propanetriol at a mass ratioof 2:1:1, dilute with physiological saline, use acetic acid to adjust topH 4.0, and obtain an MAP hydrogel disinfecting product, wherein the MAPconcentration is 5.0 mg/ml.

Select 15 patients of shingles, it is required that the affected areasare greater than 1% TBSA, the patients have a pain score >4, and theyare diagnosed by dermatologists before joining the study. Apply theabove MAP hydrogel disinfecting product on the affected part for 4 timesper day and at a dose that can evenly cover the affected part. Aftersprayed with the MAP hydrogel disinfecting product, the pain at theaffected part subsides within 1 to 8 min (onset time), and the durationof pain relief can last 2.2 to 5.0 h. After 5 days of continuous use,the duration of pain relief is extended to 12-15 h, and the use intervalis extended. After 7 days of continuous application of the MAP hydrogeldisinfecting product, erythema and blisters of shingles on 10 patientsdisappear, and their skin lesions heal. After 10 days, erythema andblisters disappear for the other 5 patients, and their skin lesions heal(see FIG. 7).

TABLE 7 Average onset time (min) 6.2 ± 1.8 Average VAS prior to use 5.9± 1.3 Average VAS after use 1.0 ± 0.6 Average itching relief 13.6 ± 1.3 duration (h) Average healing time (d) 7.9 ± 1.4

EXAMPLE 9 Use of MAP Liquid Cosmetic in Scar Pain Relief Treatment

Mix an MAP solution with sodium alginate and glycerin at a ratio of3:2:1 to prepare a formulation, use citric acid to adjust to pH 4.2, andobtain an MAP liquid drug, wherein the MAP concentration is 10 mg/ml.

Select 16 patients with post-operative scar pain, there is no limitationto the position of the scars, but the scar pain score must be ≥4 (theVAS scoring method is used to score the patients' pain). The patientscan join the groups for test only after being diagnosed by plastic &reconstructive surgeons. Apply the MAP liquid cosmetic above at theaffected part for 1 time per day. After applied with the MAP liquidcosmetic, the pain subsides at the affected part within 3 min, and theduration of pain relief can last for 9 to 15 h on the 1st day of thedrug use. After 5 days of continuous application, the duration of painrelief is extended to 48-96 h, and at the same time, inflammatorysymptoms of the scars, such as redness and swelling, subside.

EXAMPLE 10 Use of MAP Liquid Healthcare Product in Scar Pain ReliefTreatment

Take an MAP solution, mix with propanediol at a ratio of 2:1, use aceticacid to adjust to pH 4.0, and obtain an MAP liquid healthcare product,wherein the MAP concentration is 10 mg/ml.

Gather 10 patients with post-operative scar pain, there is no limitationto the position of the scars, but the scar pain score must be ≥4 (theVAS scoring method is used to score the patients' pain). The patientscan join the groups for test only after being diagnosed by plastic &reconstructive surgeons. The patients are randomly divided into acontrol group and a test group, who apply physiological saline and theabove MAP liquid healthcare product, respectively, at the affected partfor 1 time per day. After spraying the MAP liquid healthcare product,record pain mitigation situations at Days 0, 3, 7 and 13, for the testgroup, the pain decreases from 5.3 when the group begins to 0.7 afterthe use, and the p value is 0.017 compared with the control group thatdecreases from 6.1 to 3.1, which is statistically significant (α=0.05)(see FIG. 2). It proves that the MAP liquid healthcare product accordingto the present invention can mitigate the pain caused by shingles.

EXAMPLE 11 Use of MAP Liquid Medical Device in Treatment of OperativeIncisions

Take an MAP solution, dilute with a borate aqueous solution to obtain anMAP liquid formulation, and the pH is 5.5, wherein the MAP concentrationis 2.5 mg/ml.

Gather 20 patients, whose incisions are stitched up with surgicalsutures after abdominal operations, for test. The patients are diagnosedby surgeons and then join the groups. They are randomly divided into twogroups, the test group is treated with the above MAP liquid medicaldevice, and the control group is treated with physiological saline.Spray to the affected part of the selected patients at 8 h after thesurgery for 4 times per day. After sprayed with the MAP liquid medicaldevice, 10 patients keep the body positions unchanged, and the pain ismitigated significantly within 20 min, the visual analogue VAS scoregoes from 7.0-9.0 prior to the use down to 2.0-3.0. After sprayed withphysiological saline, the visual VAS scores of the 10 patients do notchange, which does not show pain suppression.

The curing period of operative incisions of the 10 patients who use theMAP liquid medical device according to the present invention is 4 days,and there is no redness or swelling on the wound edge. The curing periodof operative incisions of the 10 patients who use physiological salineis 6 days, and on Day 6, there is still slight redness and swelling onthe wound edge (see Table 8).

TABLE 8 Test group Control group Average onset time (min) 15.6 ± 3.7  Nomitigation Average VAS prior to use 8.2 ± 1.8 8.0 ± 1.5 Average VASafter use 2.4 ± 0.5 8.0 ± 0.6 Average pain relief duration (h) 8.6 ± 1.1None Average healing time (d) 3.9 ± 0.4 6.2 ± 0.7

EXAMPLE 12 Use of MAP Hydrogel Disinfecting Product in Treatment ofOperative Incisions

Take an MAP solution, add carboxymethyl cellulose and glycerin at avolumetric ratio of 2:1:1, and obtain an MAP hydrogel disinfectingproduct, wherein the MAP concentration is 2.5 mg/ml.

Gather 20 patients, whose incisions are stitched up with surgicalsutures after abdominal operations, for test. The patients are diagnosedby surgeons and then join the groups. They are randomly divided into twogroups, the test group is treated with the above MAP hydrogeldisinfecting product, and the control group is treated with a blank gelprepared by mixing carboxymethyl cellulose and glycerin. Spray to theaffected part of the selected patients at 8 h after the surgery for 4times per day. After applied with the MAP gel disinfecting product, 10patients keep the body positions unchanged, and the pain is mitigatedsignificantly within 18 min, the visual analogue VAS score goes from7.0-9.0 prior to the use down to 2.0-3.0. After applied with the blankgel, the visual VAS scores of the 10 patients do not change, which doesnot show pain suppression.

The curing period of operative incisions of the 10 patients who use theMAP gel disinfecting product according to the present invention is 4days, and there is no redness or swelling on the wound edge. The curingperiod of operative incisions of the 10 patients who use physiologicalsaline is 6 days, and on Day 6, there is still slight redness andswelling on the wound edge (see Table 9).

TABLE 9 Test group Control group Average onset time (min) 14.0 ± 2.9  Nomitigation Average VAS prior to use 8.1 ± 1.6 8.0 ± 1.2 Average VASafter use 2.6 ± 0.8 7.8 ± 0.4 Average pain relief duration (h) 8.9 ± 1.6None Average healing time (d) 3.5 ± 0.4 6.0 ± 0.8

EXAMPLE 13 Use of MAP Liquid Medical Device in Treatment of Chronic SkinUlcers

Take an MAP freeze-dried powder, use physiological saline to prepare a1.0 mg/ml aqueous solution, use acetic acid to adjust pH to 4.8, andobtain an MAP liquid medical device.

Gather 10 patients with chronic skin ulcers caused by skin inflammationor scars, the ulcer areas are between 15 and 20 square centimeters, withmanifestations of red and swollen wound edges and failure of the woundsurface to heal for more than 3 months. The patients join the groups fortest after being diagnosed by plastic & reconstructive surgeons. Spraythe MAP liquid medical device above for the selected patients for 2times per day. After 10 days of use, 8 patients have the redness andswelling of the wound edge mitigated. After 16 days of use, 3 patientshave the wound surface healed. After 21 days of use, the remaining 10patients have the wound surface healed (see FIG. 3).

EXAMPLE 14 Use of MAP Lotion Disinfecting Product in Treatment ofChronic Skin Ulcers

Take an MAP solution, mix with propanetriol at a ratio of 1:1, useacetic acid to adjust to pH 4.8, and obtain an MAP lotion disinfectingproduct.

Gather 10 patients with chronic skin ulcers caused by skin inflammationor scars, the ulcer areas are between 15 and 20 cm², with manifestationsof red and swollen wound edges and failure of the wound surface to healfor more than 3 months. The patients join the groups for test afterbeing diagnosed by plastic & reconstructive surgeons. Spray the MAPlotion disinfecting product above for the selected patients for 2 timesper day. All 10 patients have the chronic skin ulcers healed with anaverage healing time of 20.2±3.7 days. The wound base is covered by newepithelial tissues with no exudation at the surface.

EXAMPLE 15 Use of MAP Mask Cosmetic in Treatment of Coarse Pores

Mix an MAP solution with Carrageenan and agar at a ratio of 2:2:1 toobtain an MAP mask stock solution, wherein the MAP concentration is 2.0mg/ml. Take 20 ml of the MAP mask stock solution, and form an MAP maskcosmetic on silk paper.

Gather 15 patients who have coarse pores due to the use of color makeup,environmental pollution and other reasons, and who are diagnosed bydermatologists to have coarse pores. They have the manifestation ofcoarse pores and characterizations of inflammation, such as slightredness and swelling in the surrounding area.

Use the above MAP mask cosmetic once every other day, apply continuouslyfor 25 min and then take it away, for a total of 10 times of use. On Day7 of the application, the slight redness and swelling surrounding thepores are mitigated for all patients, and on Day 20, the pores shrink tonormal, and there is no characterization of inflammation.

EXAMPLE 16 Use of MAP Mask Medical Device in Treatment of Coarse Pores

Take a 1.0 mg/ml MAP solution as a mask stock solution, take 20 ml ofthe MAP mask stock solution, and form an MAP mask medical device on silkpaper.

Gather 10 patients who have coarse pores due to the use of color makeup,environmental pollution and other reasons, and who are diagnosed bydermatologists to have coarse pores. They have the manifestation ofcoarse pores and characterizations of inflammation, such as slightredness and swelling in the surrounding area.

Use the above MAP mask medical device once per day, apply continuouslyfor 25 min and then take it away, for a total of 10 times of use. On Day6 of the application, the slight redness and swelling surrounding thepores are mitigated for all patients, and on Day 18, the pores shrink tonormal, and there is no characterization of inflammation.

EXAMPLE 17 Use of MAP Patch Medical Device in Treatment of Drug Rash(Dermatitis Medicamentosa)

Take an MAP solution, mix with polyvinyl alcohol, Guar gum, polyethyleneglycol, and glycerin at a ratio of 2:1:1:0.2:0.2, use acetic acid toadjust to pH 6.5, and prepare an MAP patch stock solution, wherein theMAP concentration is 3.5 mg/ml. Take 25 ml of the MAP patch stocksolution to combine with a non-woven fabric to form an MAP patch medicaldevice.

Gather 24 patients of drug rash, the affected area is greater than 1% ofthe body surface area and the manifestation is red papules. All patientsare diagnosed by dermatologists, fill up an informed consent form andthen join the study. Use the above MAP patch medical device once perday, apply continuously for 30 min and then take it away. On Day 1 ofthe application, the itchy degree of the affected parts of the 24patients begins to subside, and the visual analogue VAS score goes from6.0-9.0 down to 2.0-3.0.

After 7 days of use, 8 patients have red papules completely disappeared.After 21 days of use, the remaining 16 patients have red papulescompletely disappeared (see Table 10).

TABLE 10 Average VAS prior to use 8.1 ± 1.5 Average VAS after use 2.4 ±0.6 Average healing time (d) 17.9 ± 2.4 

EXAMPLE 18 Use of MAP Liquid Cosmetic in Treatment of Drug Rash(Dermatitis Medicamentosa)

Take an MAP solution, use acetic acid to adjust to pH 6.0, and obtain anMAP liquid cosmetic, wherein the MAP concentration is 1.5 mg/ml.

Gather 10 patients of drug rash, the affected area is greater than 1% ofthe body surface area and the manifestation is red papules. All patientsare diagnosed by dermatologists, fill up an informed consent form andthen join the study. Apply the MAP liquid cosmetic above 1 time in themorning and 1 time in the evening every day. On Day 1 of the use, theitchy degree of the affected parts of the 10 patients begins to subside,and the visual analogue VAS score goes from 7.0-9.0 down to 2.0-3.0.After 8 days of use, 5 patients have red papules completely disappeared.After 17 days of use, the remaining 5 patients have red papulescompletely disappeared (see Table 11).

TABLE 11 Average VAS prior to use 8.6 ± 1.9 Average VAS after use 2.3 ±0.8 Average healing time (d) 13.5 ± 2.7 

EXAMPLE 19 Use of MAP Liquid Medical Device in Treatment of Psoriasis

Take an MAP solution, use acetic acid to adjust to pH 5.0, and obtain anMAP liquid medical device, wherein the MAP concentration is 1.5 mg/ml.

Gather 10 patients of psoriasis, the affected area is greater than 2% ofthe body surface area, and the manifestation is erythema with clearboundaries and various shapes and sizes, which are surrounded byinflammatory flush. There is slight infiltration and thickening, and thesurface is covered by multiple layers of silver-white scales. It is easyto scratch off the scales, and when the scales are cleaned off, there isa translucent thin film that is light red and bright. If the thin filmis broken, slight bleeding can be observed. All patients are diagnosedby dermatologists, fill up an informed consent form and then join thestudy. Use the MAP liquid medical device above for 3 times per day. OnDay 1 of the use, the itchy degree of the affected parts of the 10patients begins to subside, and the visual analogue VAS score goes from6.0-7.5 down to 2.0-3.0. After 10 days of use, 3 patients have erythemacompletely disappeared. After 20 days of use, the remaining 7 patientshave erythema completely disappeared (see Table 12).

TABLE 12 Average VAS prior to use 7.0 ± 0.5 Average VAS after use 2.4 ±0.7 Average healing time (d) 16.4 ± 3.1 

EXAMPLE 20 Use of MAP Gel Drug in Treatment of Psoriasis

Take an MAP solution, mix with Carbomer, Carrageenan and propanetriol ata mass ratio of 1:2:1:1, use acetic acid to adjust to pH 5.0, and obtainan MAP gel drug, wherein the MAP concentration is 1.0 mg/ml.

Gather 10 patients of psoriasis, the affected area is greater than 2% ofthe body surface area, and the manifestation is erythema with clearboundaries and various shapes and sizes, which are surrounded byinflammatory flush. There is slight infiltration and thickening, and thesurface is covered by multiple layers of silver-white scales. It is easyto scratch off the scales, and when the scales are cleaned off, there isa translucent thin film that is light red and bright. If the thin filmis broken, slight bleeding can be observed. All patients are diagnosedby dermatologists, fill up an informed consent form and then join thestudy. Apply the MAP gel drug above for 3 times per day. On Day 1 of theuse, the itchy degree of the affected parts of the 10 patients begins tosubside, and the visual analogue VAS score goes from 6.5-7.8 down to2.0-3.0. After 13 days of use, 5 patients have erythema completelydisappeared. After 20 days of use, the remaining 5 patients haveerythema completely disappeared (see Table 13).

TABLE 13 Average VAS prior to use 7.1 ± 0.6 Average VAS after use 2.3 ±0.9 Average healing time (d) 15.6 ± 2.7 

EXAMPLE 21 Use of MAP Liquid Medical Device in Treatment of SeborrheicDermatitis

Take an MAP solution, use acetic acid to adjust to pH 5.0, and obtain anMAP liquid medical device, wherein the MAP concentration is 1.5 mg/ml.Pour the product into a pressure comb that can store liquids, and usethe pressure comb to apply the MAP liquid medical device onto the scalp.

Gather 10 patients of seborrheic dermatitis, there is no limitation tothe area of affected parts. The early manifestation is inflammatorypapules around follicles. Subsequently as the disease develops, theybecome dark red patches that have relatively clear boundaries and areslightly yellow, which are covered by greasy scales or crusts. Thepatients feel slightly itching. All patients are diagnosed bydermatologists and then join the study. Use the MAP liquid medicaldevice above for 3 times per day.

On Day 1 of the use, the itchy degree of the affected parts of the 10patients begins to subside, and the visual analogue VAS score goes from6.0-7.5 down to 2.0-3.0. After 10 days of use, 3 patients have erythemacompletely disappeared. After 20 days of use, the remaining 7 patientshave erythema completely disappeared (see Table 14).

TABLE 14 Average VAS prior to use 7.0 ± 0.5 Average VAS after use 2.4 ±0.7 Average healing time (d) 16.4 ± 3.1 

EXAMPLE 22 Use of MAP Hydrogel Cosmetic in Treatment of SeborrheicDermatitis

Take an MAP solution, add carboxymethyl cellulose and Xanthan gum at amass ratio of 2:1:1, and obtain an MAP hydrogel cosmetic, wherein theMAP concentration is 1.5 mg/ml.

Gather 10 patients of seborrheic dermatitis, there is no limitation tothe area of affected parts. The early manifestation is inflammatorypapules around follicles. Subsequently as the disease develops, theybecome dark red patches that have relatively clear boundaries and areslightly yellow, which are covered by greasy scales or crusts. Thepatients feel slightly itching. All patients are diagnosed bydermatologists and then join the study. Use the MAP hydrogel cosmeticabove for 3 times per day. On Day 5 of the use, the itching of all theaffected parts of the 10 patients subside, the inflammatory papulesbecome lighter in color, and the patch area has a shrinking tendency.After 9 days of use, all the 10 patients have seborrheic dermatitishealed, and erythema completely disappear.

EXAMPLE 23 Use of MAP Liquid Medical Device in Hair Transplant

Take an MAP solution, use acetic acid to adjust to pH 5.0, and obtain anMAP liquid medical device, wherein the MAP concentration is 1.0 mg/ml.

Gather 10 patients of male-pattern hair loss as diagnosed by plastic &reconstructive surgeons for artificial hair transplantation. Theobservation area of hair transplant is 1% of the body surface area. Testgroup: Prior to transplantation, 5 patients use the MAP liquid medicaldevice above, and artificial hair is transplanted after 30 min. Afterhair transplant, spray the MAP medical device for 2 times per day.Control group: Prior to transplantation, spray physiological saline on 5patients as the control, and after hair transplant, spray physiologicalsaline for 2 times per day.

For the patients in the test group that use the MAP liquid medicaldevice according to the present invention, the percent of successfulhair transplant area in the overall hair transplant area is 95.1%±2.2%;for the patients in the control group that use physiological saline, thepercent of successful hair transplant area in the overall hairtransplant area is 72.8%±1.7%. It shows that MAP increases the successrate of hair transplant.

EXAMPLE 24 Use of MAP Liquid Medical Device in Skin Grafting

Take an MAP solution, use acetic acid to adjust to pH 5.5, and obtain anMAP liquid medical device, wherein the MAP concentration is 1.2 mg/ml.

Gather 10 patients of degree III burns as diagnosed by burn surgeons,and use the autologous skin grafting for treatment. The observation areaof skin grafting is 1% of the body surface area. Test group: Prior toskin grafting, 5 patients use the MAP liquid medical device above, andautologous particulate skin is grafted after 3 min. After skin grafting,spray the MAP medical device again, and provide a protection by coveringafter 3 min. Control group: Prior to skin grafting, spray physiologicalsaline on 5 patients as the control, and after skin grafting, sprayphysiological saline again. Provide a protection by covering after 3min.

For the patients in the test group that use the MAP liquid medicaldevice according to the present invention, the percent of successfulskin grafting area in the overall skin grafting area is 89.3%±1.9%; forthe patients in the control group that use physiological saline, thepercent of successful skin grafting area in the overall skin graftingarea is 62.4%±3.2%. It shows that MAP increases the success rate of skingrafting.

EXAMPLE 25 Use of MAP Liquid Medical Device in Male-Pattern Hair Loss

Take an MAP solution, use acetic acid to adjust to pH 4.5, and obtain anMAP liquid medical device, wherein the MAP concentration is 1.0 mg/ml.

Gather 10 patients of male-pattern hair loss as diagnosed bydermatologists. The manifestations include excess sebum secretion on thescalp, partial follicular necrosis, medium hair loss, and a need to washhair every day.

Select 3 cm² to count the number of follicles before using the product.Wash the hair, use the MAP liquid medical device above for the 1st time,2 times per day, and for each time, evenly spray to the entire scalp,and use continuously for 90 days. Chief complaints of the 10 patients:after the 1st time use, the sebum secretion decreases, and it is nolonger necessary to wash hair every day. The product has an effect oncontrolling the oil. After 90 days of continuous use, count the numberof follicles in the selected area again, and the number of follicles isincreased by 35%±2.3%.

It shows that the MAP product can, on one hand, inhibit the excess sebumsecretion in male-pattern hair loss, and on the other hand, repair dyingfollicles and treat hair loss.

1.-16. (canceled)
 17. A method for treating inflammation caused by aninflammatory skin disease, the method comprising: administering to anindividual having an inflammatory skin disease an effective amount of acomposition comprising a mussel adhesive protein (“MAP”), wherein saidadministering treats inflammation caused by the inflammatory skindisease.
 18. The method according to claim 17, wherein the MAP comprisesone or more of the sub-types selected from the group: Mytilus edulisfoot protein (mefp) subtypes mefp-1, mefp-2, mefp-3, mefp-4, mefp-5, andmefp-6; collagens pre-COL-P, pre-COL-D, pre-COL-NG; and mussel feetmatrix proteins PTMP and DTMP.
 19. The method according to claim 17,wherein the MAP comprises one or more of the sub-types selected from thegroup mefp-1, mefp-2, mefp-3, mefp-4, mefp-5 and mefp-6.
 20. The methodaccording to claim 19, wherein the MAP comprises mefp-1.
 21. The methodaccording to claim 17, wherein the MAP is present in the composition ata concentration of 0.1 to 15.0 mg/ml.
 22. The method according to claim17, wherein the composition is a liquid formulation, a gel formulation,a lotion, a paste, or a foam formulation, or the composition isadministered in the form of a therapy patch.
 23. The method according toclaim 17, wherein the composition has a pH in the range of 1.0 to 7.0.24. The method according to claim 17, wherein the composition has a pHin the range of 3.0 to 6.5.
 25. The method according to claim 17,wherein the inflammation is skin inflammation caused by dermatitis,eczema, skin ulcer, herpes, psoriasis, erythema multiforme, chemo rash,skin cancer, folliculitis, hives or drug rash.
 26. The method accordingto claim 17, wherein the inflammation is skin inflammation caused bypolymorphous sunlight eruption, pathological hair loss (including hairtransplant), regular acne or acne rosacea.
 27. The method according toclaim 17, wherein the inflammation is skin inflammation caused byexternal otitis.
 28. The method according to claim 17, wherein thecomposition is suitable for external skin application.
 29. The methodaccording to claim 17, wherein the composition is a medicine, a cosmeticpreparation, a disinfecting product, a healthcare product, a food or ahousehold chemical.
 30. The method according to claim 17, wherein thecomposition is a foam formulation comprising MAP as the main activeingredient and a foaming agent matrix material, said foaming agentmatrix material being one or any combination of hydroxypropyl methylcellulose, gelatin, polyethylene glycol, sodium dodecyl sulfate, sodiumfatty alcohol polyoxyethylene ether sulfonate, corn gluten powder, andacrylamide.